On June 11, 2021 ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, reported that new data presented by John Daly from the academic lab of CSO, Prof. Michael O’Dwyer at the Annual European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress illustrating the merit of knocking out the checkpoint inhibitory receptor for CD96 on NK cells in the context of MM (Press release, ONK Therapeutics, JUN 11, 2021, View Source [SID1234583898]).
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The data is based on research studies carried out at the National University of Ireland, Galway (NUI Galway), College of Medicine, Nursing and Health Sciences, by Prof. O’Dwyer’s academic research group.
Contradictory data had previously shown that CD96 could be both an activating and an inhibitory receptor on human NK cells, depending on the tumor type being examined. The data presented during the poster presentation demonstrate conclusively that in the case of MM cells expressing CD155, CD96 is a human NK cell inhibitory receptor, regulating both cytotoxicity and cytokine release. Experiments using CRISPR/Cas9-mediated KO of CD96 in primary NK cells resulted in enhanced cytotoxicity and cytokine release compared to controls. Studies carried out in parallel also demonstrated a similar beneficial effect of CRISPR/Cas9-mediated KO of TIGIT in primary NK cells.
Furthermore, NK cells obtained from MM patient bone marrow had particularly high levels of CD96 expression, suggesting NK cells in the bone marrow of MM patients are more likely to be susceptible to CD155 mediated immune-evasion.
These new insights support knocking out inhibitory checkpoint receptors, including CD96 KO and TIGIT KO as a promising approach to improving the functionality of off-the-shelf engineered NK cell therapies for the treatment of cancer.
E-poster presentation title: Knockout of CD96 or TIGIT using CRISPR/Cas9 enhances NK induced
cytotoxicity and cytokine production in the presence of CD155 expressing myeloma cells.
Author(s)/Presenters: John Daly, Mark Gurney, Michael O’Dwyer.
Session title: Myeloma and other monoclonal gammopathies – Biology & Translational Research.
Abstract number: EP941
Date and Time: Available on the virtual platform as an e-poster Friday, June 11 at 9:00 CEST.
Download a copy HERE.
Chris Nowers, ONK Therapeutics’ CEO said, "The studies carried out by Prof. O’Dwyer’s academic research group are expanding our deep understanding of NK cell biology and are helping to confirm certain gene constructs and edits that will enhance NK cell cytotoxicity, cytokine production and persistence in the tumor microenvironment. Gene edited NK cells lacking CD96 and/or TIGIT could therefore be beneficial for treating CD155 expressing malignancies, such as Multiple Myeloma."
ONK Therapeutics was formed based on technology and intellectual property developed at NUI Galway by Prof. O’Dwyer. The Company is developing off-the-shelf, optimized NK cell therapies for cancer that utilize dual-targeting of the death receptor pathway in addition to incorporating a CAR, along with further strategies that utilize novel gene editing approaches to enhance persistence, metabolic profile, and cytotoxic potential. ONK has exclusive licenses to a broad intellectual property (IP) against a wide range of NK cell checkpoints, including CD96 and TIGIT.